In Vitro Effects of the Selected Brominated Flame Retardants on the Ovarian Follicular Cell Steroidogenesis

Introduction Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs can accumulate in the environment and have been detected in wildlife and in human adipose tissue and plasma samples. The congeners 2,2 ́,4,4 ́tetraBDE (BDE-47), 2,2 ́,4,4 ́,5-pentaBDE (BDE-99), and 2,2 ́,4,4 ́,6-pentaBDE (BDE-100) are generally the dominant congeners found in wildlife and humans. BDE209, the main congener (> 97%) in the Deca-BDE formulation, was detected only in a minority of the samples and always at concentrations around the limit of detection. Surprisingly there is a lack of data showing a direct action of brominated biphenyls on ovarian function and especially on the ovarian steroidogenesis. In our laboratory, we collect follicular cells from porcine ovary excised from normal, hormone-untreated animals, to study the direct effects of xenobiotics on ovarian steroidogenesis. Pigs exhibit a wide range of physiological similarities to humans, notably, in metabolism, making porcine cells a valuable tool for studying potential human toxicants. We use a co-culture model of theca and granulosa cells cultured at the ratio existing in vivo in the follicles. This model is more physiological than the culture of individual cell types or cell lines. In this co-culture model, both cell types retain their developmental and follicular stage-specific ability to secrete steroids (estradiol, testosterone and progesterone). This model is, therefore, ideally suited for investigation of the effects of xenobiotics on hormone production by ovarian follicles. Surprisingly, data concerning direct action of a BDEs on ovarian function are scare. The purpose of this research was to 1) determine estrogenic activity of BDE-47, BDE-99, BDE-100, BDE-209 in ovarian follicular cells , 2) determine their action on cell proliferation, viability and apoptosis.